What Is GHK-Cu? Copper Peptide Chemistry Explained
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Up here in Michigan, the Keweenaw Peninsula built a whole history on copper. So it's fitting that one of the compounds we carry, GHK-Cu, is a peptide with a copper ion held right in the middle of it. This post sticks to the chemistry: what the molecule is, how it holds onto copper, where it was first found, and how labs check that a sample is what the label says.
What is GHK?
GHK is a tripeptide, a chain of just three amino acids: glycine, L-histidine and L-lysine, written Gly-His-Lys. Its full name is glycyl-L-histidyl-L-lysine. [1][3]
PubChem lists the free peptide (CID 73587) with:
- Molecular formula: C14H24N6O4
- Molecular weight: 340.38 g/mol
- Monoisotopic mass: about 340.186 Da [1]
What is GHK-Cu?
GHK-Cu is GHK bound to a copper(II) ion (Cu2+). PubChem's record for the copper complex (CID 71587328, listed as "prezatide copper") gives:
- Molecular formula: C14H23CuN6O4+
- Molecular weight: 402.92 g/mol
- Monoisotopic mass: about 402.108 Da [2]
Notice the formula loses one hydrogen compared with the free peptide. That fits with the peptide giving up a proton as it wraps around the metal.
How GHK binds copper
GHK is a high-affinity copper(II) binder. A 2011 structural study by Hureau and colleagues, using X-ray crystallography plus EPR, X-ray absorption and NMR spectroscopy, summarized how the complex is put together: [4]
- In solution, [Cu(II)(GHK)] is a monomer with three nitrogen atoms holding the copper: the N-terminal amine (NH2) of glycine, a deprotonated amide ("amidyl") nitrogen from the peptide backbone, and a nitrogen from histidine's imidazole ring.
- The fourth spot around the copper is taken by a loosely bound oxygen. In the solid crystal it comes from a neighboring carboxylate group, and the solid-state structure is a dimer.
- Copper swaps quickly between GHK molecules, unlike in some related copper-binding peptides.
Back in 1980, Pickart and co-workers had already pointed out the resemblance between GHK and the copper-transport site on albumin, where copper sits on a histidine next to a basic amino acid. [3]
A short discovery history
GHK was first described by Loren Pickart, who reported a tripeptide isolated from human plasma in his 1973 doctoral thesis at the University of California, San Francisco. [5] In a 1980 Nature paper, Pickart and colleagues reported that during isolation the peptide came out with roughly equimolar copper, that it readily forms complexes with copper(II), and that it may function as a copper-transport factor in cultured cells. [3] (That paper abbreviates the peptide "GHL"; today it's almost always written GHK, using the one-letter code for lysine.)
Where GHK occurs naturally
GHK is a naturally occurring human peptide found in blood plasma. [4][5] A 2018 review by Pickart and Margolina cites a plasma level of about 200 ng/mL at age 20. [5] The same review notes that the Gly-His-Lys sequence also appears inside larger proteins, including the alpha-2 chain of type I collagen and the protein SPARC, and can be released when those proteins are broken down. [5]
How labs confirm identity and purity
For a small synthetic peptide like this one, two techniques do most of the work: [6]
Identity: mass spectrometry (MS)
Mass spectrometry measures the mass of molecules in a sample. For GHK-Cu, the analyst compares the measured mass with the expected value, about 340.19 Da for free GHK or about 402.11 Da for the copper complex. [1][2] If the right mass shows up, you have evidence the molecule is what it should be. If it doesn't, something is wrong.
Purity: high-performance liquid chromatography (HPLC)
Reversed-phase HPLC separates the target peptide from closely related impurities and breakdown products. The main peak's share of the total signal is usually reported as percent purity. Peptide labs often pair the two in a single run (LC-MS), so each peak can be checked by mass too. [6]
One caution: MS confirms what is present and HPLC estimates how much of it is the target, but neither replaces confirming the report belongs to the lot you actually have.
How we handle it at Mibio-ops
We sell GHK-Cu as Keweenaw Copper Well. Documentation for each lot is available to verified purchasers.
FAQ
What does GHK stand for?
The one-letter amino acid codes for glycine (G), histidine (H) and lysine (K): glycyl-L-histidyl-L-lysine. [1]
What is the molecular weight of GHK-Cu?
PubChem lists 402.92 g/mol for the copper complex and 340.38 g/mol for free GHK. [1][2]
Who discovered GHK?
Loren Pickart, who first described it from human plasma in 1973. [3][5]
Is GHK-Cu the same as "copper peptide"?
"Copper peptide" is a loose label that can cover several copper-peptide complexes. GHK-Cu is the specific Gly-His-Lys copper(II) complex. Check the name, formula and mass on any document.
For laboratory research use only. Not for human or veterinary use.
Sources
- PubChem. Glycyl-histidyl-lysine, CID 73587. National Library of Medicine. https://pubchem.ncbi.nlm.nih.gov/compound/73587
- PubChem. Prezatide copper (GHK-Cu), CID 71587328. National Library of Medicine. https://pubchem.ncbi.nlm.nih.gov/compound/71587328
- Pickart L, Freedman JH, Loker WJ, et al. "Growth-modulating plasma tripeptide may function by facilitating copper uptake into cells." Nature. 1980;288:715โ717. doi:10.1038/288715a0. https://pubmed.ncbi.nlm.nih.gov/7453802/
- Hureau C, Eury H, Guillot R, et al. "X-ray and solution structures of Cu(II) GHK and Cu(II) DAHK complexes: influence on their redox properties." Chemistry โ A European Journal. 2011;17(36):10151โ10160. doi:10.1002/chem.201100751. https://pubmed.ncbi.nlm.nih.gov/21780203/
- Pickart L, Margolina A. International Journal of Molecular Sciences. 2018;19(7):1987. doi:10.3390/ijms19071987. https://pmc.ncbi.nlm.nih.gov/articles/PMC6073405/
- Sharma N, Kukreja D, Giri T, Kumar S, Shah RP. "Synthetic pharmaceutical peptides characterization by chromatography principles and method development." Journal of Separation Science. 2022;45(13):2200โ2216. doi:10.1002/jssc.202101034. https://pubmed.ncbi.nlm.nih.gov/35460196/
